Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTD7DG7V)

• DOT Name: Transmembrane protein 217 (TMEM217)
• Gene Name: TMEM217
• Related Disease:
  Diabetic retinopathy
  X-linked reticulate pigmentary disorder
• UniProt ID: TM217_HUMAN
• Pfam ID: PF15049
• Sequence:
  MKQQQWCGMTAKMGTVLSGVFTIMAVDMYLIFEQKHLGNGSCTEITPKYRGASNIINNFI
  ICWSFKIVLFLSFITILISCFLLYSVYAQIFRGLVIYIVWIFFYETANVVIQILTNNDFD
  IKEVRIMRWFGLVSRTVMHCFWMFFVINYAHITYKNRSQGNIISYKRRISTAEILHSRNK
  RLSISSGFSGSHLESQYFERQSFHTSIFTCLSPVPSSAPSTCRYTIDVC

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Diabetic retinopathy	DISHGUJM	Definitive	Biomarker	[1]
X-linked reticulate pigmentary disorder	DIS0RB5A	Strong	Genetic Variation	[2]

9 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Transmembrane protein 217 (TMEM217).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Transmembrane protein 217 (TMEM217).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Transmembrane protein 217 (TMEM217).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Transmembrane protein 217 (TMEM217).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Transmembrane protein 217 (TMEM217).	[7]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Transmembrane protein 217 (TMEM217).	[8]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Transmembrane protein 217 (TMEM217).	[9]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Transmembrane protein 217 (TMEM217).	[11]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID increases the expression of Transmembrane protein 217 (TMEM217).	[12]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Transmembrane protein 217 (TMEM217).	[10]

References

• [1] Association of genes on chromosome 6, GRIK2 , TMEM217 and TMEM63B (linked to MRPL14 ) with diabetic retinopathy.Ophthalmologica. 2013;229(1):54-60. doi: 10.1159/000342616. Epub 2012 Sep 28.
• [2] Whole exome sequencing identification of novel candidate genes in patients with proliferative diabetic retinopathy.Vision Res. 2017 Oct;139:168-176. doi: 10.1016/j.visres.2017.03.007. Epub 2017 May 9.
• [3] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [4] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [5] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [8] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [9] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [10] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [11] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [12] Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.